In recent years, managements of opportunistic infections have become more and more significant more than ever because of an increase in the number of elderly people and immunocompromised patients as a result of advanced chemotherapies or the like. As demonstrated by the fact that opportunistic infections are occurring one after another by different weakly avirulent bacteria, it is shown that the problem of infectious disease will not ends as long as there are underlying diseases that diminish the immune functions of patients. Consequently, new strategies for infectious diseases control, including the problem of resistant bacteria, will be one of the important issues in the soon-to-come aged society.
In the field of antifungal agents, heretofore, for instance, amphotericine B which is based on a polyene skeleton, fluconazole, itraconazole and voriconazole which are based on an azole skeleton, or the like, have been developed for the treatment of deep seated mycoses. Among pre-existing drugs already available commercially are many agents having similar mechanism of action, and currently, the appearance of azole-resistant fungi or the like has been problems.
In recent years, as a 1,3-β-glucan synthetase inhibitor with a novel mechanism, naturally occurring compound-derived cyclic hexapeptides caspofungin and micafungin or the like, have been developed; however, from the fact that these agents only exist in injectable form, they are not yet sufficient practically as antifungal agents.
Since there have been the situations that the pre-existing antifungal agents are insufficient for treatment of the deep seated mycoses, there is a demand and need for development of agents which are based on a novel mechanism and are of high safety.
As the prior art related to antifungal agents based on such a novel mechanism, Patent Document 1 describes heterocyclic compounds which demonstrates effects against the onset, progress, and persistence of infections by inhibiting the expression of cell wall proteins, inhibiting the cell wall assembly and also adhesion onto cells, and preventing pathogens from showing pathogenicity, with the process which transports GPI (Glycosylphosphatidylinositol)-anchored proteins to the cell wall being inhibited. However, groups of the compounds disclosed in Patent Document 1 have 2-benzyl pyridine moieties as the common structure, clearly differing structurally from compounds according to the present invention. In addition, the groups of the compounds disclosed in Patent Document 1 bear the problem that, although these compounds demonstrate activities in vitro, they are easily metabolized inside the body, or the like.
Meanwhile, there are Patent Documents 2 through 8 as the prior art that disclose structurally most similar compounds to the heterocyclic compound (I) according to the present invention. Patent Document 2 discloses N-(4-pyridyl)carboxamide derivatives having the effects as pesticides, in particular as insecticides, acaricides and nematicides. Patent Documents 3 through 6 disclose 2-aryloxy nicotinamide derivatives having phosphodiesterase 4 (PDE4) inhibitory action. Patent Document 7 discloses 6-(arylamino)nicotinamide derivatives having cannabinoid receptor modulation action and Patent Document 8 discloses 6-(aryloxy)nicotinamide derivatives having Na+/Ca2+ exchanger inhibitory action. However, Patent Documents 2 through 8 do not disclose the compounds according to the present invention. In addition, Patent Documents 2 through 8 do not describe that the compounds disclosed in these documents exhibit antifungal and antimalarial actions for Candida, Aspergillus, Cryptococcus or the like which are general fungal strains in human mycosis at all.    [Patent Document 1] International Publication No. WO 02/04626 pamphlet;    [Patent Document 2] U.S. Pat. No. 5,852,042 Specification;    [Patent Document 3] European Patent Application No. 1229034 specification;    [Patent Document 4] International Publication No. WO 02/060875 pamphlet;    [Patent Document 5] International Publication No. WO 02/060896 pamphlet;    [Patent Document 6] International Publication No. WO 03/068232 pamphlet;    [Patent Document 7] International Publication No. WO 2004/029027 pamphlet; and    [Patent Document 8] International Publication No. WO 2004/000813 pamphlet.